PXD070395-1

PXD070395 is an original dataset announced via ProteomeXchange.

Title	A group competition strategy for covalent ligand discovery
Description	As a powerful chemoproteomic tool, activity-based protein profiling (ABPP) has been extensively used for covalent ligand discovery. However, the current ABPP-based approaches are inherently based on indirect probe labeling competed by covalent ligands, and cannot directly compare the preferences of different ligands head-to-head. Herein, we report a Group Competition-based ABPP strategy (GC-ABPP) to allow the direct comparison of multiple ligands’ binding ability on a proteome-wide scale. By dividing a library of fully functionalized probes (FFPs) into different sub-groups and labeling the proteome simultaneously, the direct competition enables comparison of the labeling ability of different probes in drawing a global protein-ligand affinity metric. When it is applied to an expanded probe library, this strategy can be used iteratively to select the highest-affinity ligand toward a certain target protein in a multiple-round process. As a proof of concept, we synthesized 65 FFPs and employed the GC-ABPP to screen the ligand-protein reactivity for >6000 cysteine sites. After three rounds screening, we identified high-affinity ligands targeting BCAT2 and UGDH. Our “multiple ligands versus multiple proteins” screening paradigm demonstrates great potential for applications in covalent ligand/drug discovery.
HostingRepository	iProX
AnnounceDate	2025-11-06
AnnouncementXML	Submission_2025-12-03_23:00:05.634.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Weidi Xiao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-05 22:46:12	ID requested
⏵ 1	2025-12-03 23:00:06	announced

Dataset with its publication pending

submitter keyword: Probe, chemoproteomics

Chu Wang
contact affiliation	Peking University
contact email	chuwang@pku.edu.cn
lab head
Weidi Xiao
contact affiliation	Beijing Proteome Research Center
contact email	weidixiao@126.com
dataset submitter

iProX dataset URI